ε-caprolactam

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Groups of 10 Wistar rats/sex were exposed to a liquid aerosol of the test substance (50%, w/w) using a head-nose inhalation system.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

ε-caprolactam

EC Number:

203-313-2

EC Name:

ε-caprolactam

Cas Number:

105-60-2

Molecular formula:

C6H11NO

IUPAC Name:

azepan-2-one

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach
- Age at study initiation: 8 weeks
- Mean weight at study initiation: male 250 g (224-268 g) female 178 g (161-192 g)
- Diet (e.g. ad libitum): Kliba labor diet
- Water (e.g. ad libitum): tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other:

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose/head - inhalation system INA 20, BASF AG
- Exposure chamber volume: 55 l
- Method of holding animals in test chamber: animals were kept in the tube with muzzle projecting in the inhalation chamber
- System of generating particulates/aerosols: Generatorsystem- infusion pump INFU 362, membrane dose pump Duramat. The aerosol was generated using compressed air.
- Temperature in air chamber: 19-25 °C


TEST ATMOSPHERE
- Brief description of analytical method used: Quantitative determination of aerosol concentration was performed using gas chromatography. For this the aerosol probes were dissolved in 10ml Ethanol.
- Samples taken from breathing zone: yes
- Nominal concentrations were calculated using the substance consumption and the air volume.
- probes for particle size analysis were taken from 30 min after onset of exposure

VEHICLE
- Concentration of test material in vehicle: 50% (w/v) in water

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.25, 8.35 and 10.12 mg/l

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight of individual animals was measured before treatment and after 7 and 14 days of treatment, daily clinical inspection
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (anatomical/pathological)

Statistics:

According to the probit analysis of D.J. Finney, 1-150 (Syndics of the Cambridge University Press, 1971).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

8.16 mg/L air

95% CL:

7.2 - 9.23

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 9.6 mg/L air (analytical)

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

7.08 mg/L air (analytical)

95% CL:

5.87 - 8.1

Exp. duration:

4 h

Mortality:

Mortality was observed (see table 1).

Clinical signs:

other: Symptoms during exposure: closure of eyelid, irregular respiration, escape reaction Symptoms after exposure: dyspnoea, piloerection, intermittent respiration, bloody nose and eye discharge, tremor. Clinical signs were reversible after 5 days (low dose), 7

Body weight:

No effects on body weight gain were observed

Gross pathology:

Severe hyperemia in lungs and liver adiposis in some perished animals. No abnormalities in the sacrificed animals

Other findings:

- Histopathology: fatty degeneration in the liver and ischemic tubulonephrosis in the cortex of the kidney of 1 deceased animal. No lesions were observed in the sacrificed animals.

Any other information on results incl. tables

Table 1: Mortality of males and females.

Dose (mg/l)	Sex	Mortality within
		4 h	1 day	14 days
5.25	M	0/10	1/10	1/10
	F	0/10	1/10	1/10
8.25	M	0/10	1/10	1/10
	F	0/10	7/10	7/10
10.12	M	2/10	7/10	7/10
	F	1/10	10/10	10/10

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LC50 value for male/female rats was determined to be 8.16 mg/l.

Executive summary:

This study was performed similar to the OECD guideline 403. Rats were exposed to a liquid aerosol of the test substance using a head-nose inhalation system at analytical concentrations of 5.25, 8.35 and 10.12 mg/l for 4 hours. Exposure related mortalities were observed at all dose levels and the LC50 for male/female was determined to be 8.16 mg/l.

Observed clinical signs of toxicity were indicative for irritation (eyelid closure, irregular respiration, escape reaction during exposure and dyspnoea, piloerection, bloody nose and eye discharge and tremor after exposure). Clinical signs were reversible with 7 days post exposure.